IL-4和IFN-γ对COPD患者肺成纤维细胞HIF-1α和TGF-β1表达的影响

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Abstract Objective To investigate the synergistic regulation of interleukin 4 (IL-4) and gamma interferon (IFN-γ) in airway remodeling in patients with chronic obstructive pulmonary disease (COPD). Methods From December 2017 to August 2018, lung tissue was collected from the Department of Thoracic Surgery, Central South University, Xiangya School of Medical, Affiliated Haikou Hospital. Lung tissue samples from 16 patients with lung cancer and 12 patients with lung cancer combined with COPD were surgically removed. Lung fibroblasts were isolated and identified from normal lung tissues and lung tissues of COPD patients, respectively, and the expression levels of hypoxia-induced factor 1α (HIF-1α) and transformed growth factor β1 (TGF-β1) were detected by qRT-PCR and Western blot, lung fibroblasts were stimulated with IL-4 and IFN-γ, respectively, and the expression levels of HIF-1α and TGF-β1 were subsequently detected to evaluate the effects of IL-4 and IFN-γ on lung fibroblasts HIF-1α/TGF-β1. Results Compared with normal lung fibroblasts, mRNA levels of HIF-1α and TGF-β1 in lung fibroblasts of COPD patients were significantly increased (P ＜ 0.01). IL-4 induced increased expression of HIF-1α and TGF-β1 in lung fibroblasts (P ＜ 0.05). The expression of HIF-1α and TGF-β1 was positively correlated with the duration of IL-4 action （R2 = 0.8736，P = 0.0018；R2 = 0.8637，P = 0.0223）. IFN-γ inhibits HIF-1α and TGF-β1 expression in lung fibroblasts (P ＜ 0.05), the expression of HIF-1α and TGF-β1 was negatively correlated with IFN-gamma duration （R2 = 0.8410，P = 0.0283；R2 = 0.8142，P = 0.0361）. Conclusion IL-4 promoted the expression of HIF-1α and TGF-β1 in pulmonary fibroblasts in COPD patients. Moreover, the expression of HIF-1α and TGF-β1 was positively correlated with the duration of IL-4 action. In contrast, IFN-γ inhibited the expression of HIF-1α and TGF-β1 in pulmonary fibroblasts in COPD patients, and the expression of HIF-1α and TGF-β1 was negatively correlated with the duration of IFN-γ action.

Key words： Interleukin 4 Interferon-γ Hypoxia-induced factor 1α Transformed growth factor β1 Chronic obstructive pulmonary disease remodeling

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	ZENG Cimei1 OU Zongxing1 HUANG Denggao2 SHEN Bing1 WANG Lei1 MA Ximiao3 CAO Hui2

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ZENG Cimei1 OU Zongxing1 HUANG Denggao2 SHEN Bing1 WANG Lei1 MA Ximiao3 CAO Hui2. Effect of IL-4 and IFN-γ on the expression of HIF-1α and TGF-β1 in lung fibroblasts of COPD patients[J]. 中国医药导报, 2019, 16(29): 16-20.

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http://www.yiyaodaobao.com.cn/EN/ OR http://www.yiyaodaobao.com.cn/EN/Y2019/V16/I29/16

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